Depressive DisorderNCT01165255
Bupropion and Specific Cardiovascular Malformations
An observational study of Depressive Disorder and Pregnancy, run by GlaxoSmithKline.
Trial summary
The study is an extension of earlier work based on a retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety (Clinical study ID WWE113694) (Cole JA, Oh KS, Chiang CC… Read more about this study
- Who is it for?
- Ages 12 to 49 years, women only
- Conditions the study is for
- Depressive Disorder, Pregnancy, Smoking Cessation
- What is being tested?
- 3. Exposure to other antidepressants during the first trimester comparison cohort, 2. Exposure to bupropion outside the first trimester comparison cohort and 1. Exposure to bupropion during the first trimester
- How many people
- 7,005 participants
- Where
- No sites listed yet
- Study dates
- Jun 2010to Dec 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 49 years
- Women only
- No healthy volunteers
- Child, Adult
Study population: The study population will be the same as that used previously in the retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety. 1,213 infants born to 1,140 women (1,142 pregnancies) were exposed to bupropion during the first trimester. The comparison groups consisted of 4,753 infants born to 4,617 women (4,649 pregnancies) exposed to other anti-depressants during the first trimester, and 1,049 infants born to 1,009 women (1,009 pregnancies) exposed to bupropion outside of the first trimester. All medical and prescription claims data along with dates of health plan enrollment for these women were included. The other antidepressant sample was frequency-matched to the bupropion cohort by year of birth, and was selected irrespective of exposure to specific antidepressants.
Who may be able to join
- The inclusion criteria will be the same as that used previously in the retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety.
- All deliveries occurring between 01 January 1995 and 30 September 2004 among women ages 12 to 49 who are members of UnitedHealthcare
- Eligible for prescription benefits
- Have one or more dispensings of an antidepressant during the study period
- Continuously enrolled for at least eighteen months prior to delivery
- Women were required to have one year of continuous health plan membership before their delivery date.
- Women were also included when the associated infant remained on the insurance plan.
Who cannot join
- Members who are employees of UnitedHealthcare are excluded from the Ingenix Research Database.
About this study
The study is an extension of earlier work based on a retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety (Clinical study ID WWE113694) (Cole JA, Oh KS, Chiang CC, Walker AM, Haight BR, Modell JG. Bupropion in pregnancy and the prevalence of congenital malformations Pharmacoepidemiology and Drug Safety, 2007; 16: 474-484). The cohorts developed for the earlier work consisted of all infants born to women exposed to bupropion during the estimated first trimester and outside the first trimester, and a random sample of infants born to women exposed to other antidepressants during the first trimester between 01 January 1995 and 30 September 2004. The objectives for this study include refining of both the original first trimester bupropion cohort and the original bupropion outside the first trimester cohort into mono-therapy and mono- or poly-therapy. Exposure to other antidepressants during the first trimester will also be refined into mono-therapy and mono- or poly-therapy. With input from pediatric cardiology expert, lists of specific cardiovascular malformations and malformation groupings will be created. The groupings will be created among the refined first trimester bupropion cohort as well as in two comparison cohorts of bupropion outside the first trimester and first trimester antidepressant use (mono-therapy and mono-or poly-therapy). The prevalence in each cohort will be calculated as the number of infants with a specific cardiovascular malformation divided by the number of live born infants. Prevalence will be reported per 1,000 infants. Confidence intervals will be calculated using Wilson's approximation to exact binomial intervals when the number of cases is five or greater and exact binomial intervals when the number of cases is fewer than five. The appropriateness of further calculations will be evaluated. Where numbers permit, adjusted odds ratios for specific cardiovascular groups/malformations will be calculated and if appropriate, stratified according to maternal dispensing of medications suspected to be teratogenic. The following comparisons, if numbers permit, will be performed: 1) bupropion first trimester mono-therapy cohort versus other antidepressant first trimester mono-therapy cohort; 2) bupropion first trimester mono- or poly-therapy cohort versus other antidepressant first trimester mono- or poly-therapy cohort; 3) bupropion first trimester mono-therapy cohort versus bupropion outside of first trimester mono-therapy cohort, and 4) bupropion first trimester mono- or poly-therapy cohort versus bupropion outside of first trimester mono- or poly-therapy cohort. Adjusted odds ratios will be calculated through a generalized estimated equations form of multivariate logistic regression to account for births associated with multiple infants. The same covariates identified in the original study will be included in this re-analysis. Covariates included: diagnoses of bipolar disorder and eclampsia within one year before delivery; dispensings of lithium, phenytoin, and fluconazole within one year before delivery through the end of the first trimester; and the number of physician visits within 10 to 12 months before delivery, maternal age, geographic region of the health plan, and infant gender. If generalized estimating equation form of the logistic regression model does not converge, adjusted odds ratios will be presented from a conventional multivariate logistic model. If the conventional multivariate logistic model does not converge, only the crude odds ratio will be presented.
Read the detailed description
Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.
- Conditions
- Depressive Disorder, Pregnancy, Smoking Cessation
- Being tested
- 3. Exposure to other antidepressants during the first trimester comparison cohort, 2. Exposure to bupropion outside the first trimester comparison cohort, 1. Exposure to bupropion during the first trimester
- Keywords
- congenital malformation, cardiovascular malformation, cardiovascular defect, antidepressants, pregnancy, first trimester, Bupropion, prevalence
- Medical subject headings
- Depressive Disorder, Smoking Cessation, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3. Exposure to other antidepressants during the first trimester comparison cohortDrug
Exposure to other antidepressants during first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate dispensing of other antidepressants. Infants were classified according to maternal exposure to other antidepressants during the first trimester. The first trimester was estimated as the earliest probable conception date through 91 days (13 weeks) following the latest probable conception date (based on delivery diagnosis codes). This study will refine the exposure classifications into infants born to women who were exposed only to one type of an antidepressant ("other antidepressant monotherapy"), or more than one type of an antidepressant ("other antidepressant mono or polytherapy") during the first trimester. A woman was considered exposed if there is at least one dispensing of another antidepressant during the first trimester of pregnancy.
2. Exposure to bupropion outside the first trimester comparison cohortDrug
Exposure to bupropion outside the first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate a dispensing of bupropion. The comparison cohort ("bupropion exposure outside the first trimester") included women whose bupropion exposure occurred at least one month before the estimated date of conception and women whose bupropion exposure occurred after the first trimester, but before delivery. This study will refine the exposure classifications into infants born to women, who were exposed only to bupropion ("bupropion monotherapy"), or bupropion and another type of an antidepressant ("bupropion mono-or polytherapy") during the period outside the first trimester.
1. Exposure to bupropion during the first trimesterDrug
Exposure to bupropion during the first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate a dispensing of bupropion. Infants were classified according to maternal exposure to bupropion during the first trimester. The first trimester was estimated as the earliest probable conception date through 91 days (13 weeks) following the latest probable conception date (based on delivery diagnosis codes). This study will refine the exposure classifications into infants born to women, who were exposed only to bupropion ("bupropion monotherapy"), or bupropion and another type of an antidepressant ("bupropion mono-or polytherapy"). A woman was considered exposed in the first trimester if there was at least one dispensing of bupropion during the first trimester of pregnancy.
| Study group | Role | What they receive |
|---|---|---|
| Infants born to women who were exposed to antidepressants | Women ages 12 through 49 (as of delivery date) who were dispensed an antidepressant between 01 January 1995 and 30 September 2004 from the original Bupropion study. Receives: Drug: 3. Exposure to other antidepressants during the first trimester comparison cohort; Drug: 2. Exposure to bupropion outside the first trimester comparison cohort; Drug: 1. Exposure to bupropion during the first trimester |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequencies and prevalence estimates of specific cardiovascular malformations and malformation groupings among live infants born to women exposed to bupropion or antidepressants
Measured: As performed previously, medical and prescription claims data was assembled and the outcomes of infants in the first 9 months of life were evaluated
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2010 (estimated)
- Study startJun 2010
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive DisorderStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 7,005 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01165255
- Sponsor's protocol ID
- 114592
- Other IDs
- EPI40642, WEUSKOP4894
- Status last verified
- Jun 2017
- First submitted
- 1 Jul 2010
- Last updated
- 7 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bupropion and Specific Cardiovascular Malformations
- ClinicalTrials.gov ID
- NCT01165255
- Acronym / sponsor ID
- 114592
- Conditions
- Depressive Disorder, Pregnancy, Smoking Cessation
- Keywords
- congenital malformation, cardiovascular malformation, cardiovascular defect, antidepressants, pregnancy, first trimester, Bupropion, prevalence
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7,005 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 19 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is an extension of earlier work based on a retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety (Clinical study ID WWE113694) (Cole JA, Oh KS, Chiang CC, Walker AM, Haight BR, Modell JG. Bupropion in pregnancy and the prevalence of congenital malformations Pharmacoepidemiology and Drug Safety, 2007; 16: 474-484). The cohorts developed for the earlier work consisted of all infants born to women exposed to bupropion during the estimated first trimester and outside the first trimester, and a random sample of infants born to women exposed to other antidepressants during the first trimester between 01 January 1995 and 30 September 2004. The objectives for this study include refining of both the original first trimester bupropion cohort and the original bupropion outside the first trimester cohort into mono-therapy and mono- or poly-therapy. Exposure to other antidepressants during the first trimester will also be refined into mono-therapy and mono- or poly-therapy. With input from pediatric cardiology expert, lists of specific cardiovascular malformations and malformation groupings will be created. The groupings will be created among the refined first trimester bupropion cohort as well as in two comparison cohorts of bupropion outside the first trimester and first trimester antidepressant use (mono-therapy and mono-or poly-therapy). The prevalence in each cohort will be calculated as the number of infants with a specific cardiovascular malformation divided by the number of live born infants. Prevalence will be reported per 1,000 infants. Confidence intervals will be calculated using Wilson's approximation to exact binomial intervals when the number of cases is five or greater and exact binomial intervals when the number of cases is fewer than five. The appropriateness of further calculations will be evaluated. Where numbers permit, adjusted odds ratios for specific cardiovascular groups/malformations will be calculated and if appropriate, stratified according to maternal dispensing of medications suspected to be teratogenic. The following comparisons, if numbers permit, will be performed: 1) bupropion first trimester mono-therapy cohort versus other antidepressant first trimester mono-therapy cohort; 2) bupropion first trimester mono- or poly-therapy cohort versus other antidepressant first trimester mono- or poly-therapy cohort; 3) bupropion first trimester mono-therapy cohort versus bupropion outside of first trimester mono-therapy cohort, and 4) bupropion first trimester mono- or poly-therapy cohort versus bupropion outside of first trimester mono- or poly-therapy cohort. Adjusted odds ratios will be calculated through a generalized estimated equations form of multivariate logistic regression to account for births associated with multiple infants. The same covariates identified in the original study will be included in this re-analysis. Covariates included: diagnoses of bipolar disorder and eclampsia within one year before delivery; dispensings of lithium, phenytoin, and fluconazole within one year before delivery through the end of the first trimester; and the number of physician visits within 10 to 12 months before delivery, maternal age, geographic region of the health plan, and infant gender. If generalized estimating equation form of the logistic regression model does not converge, adjusted odds ratios will be presented from a conventional multivariate logistic model. If the conventional multivariate logistic model does not converge, only the crude odds ratio will be presented.
Detailed description
Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infants born to women who were exposed to antidepressants | – | Drug: 3. Exposure to other antidepressants during the first trimester comparison cohort, Drug: 2. Exposure to bupropion outside the first trimester comparison cohort, Drug: 1. Exposure to bupropion during the first trimesterWomen ages 12 through 49 (as of delivery date) who were dispensed an antidepressant between 01 January 1995 and 30 September 2004 from the original Bupropion study. |
Who may qualify
- Ages
- 12 to 49 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- The study population will be the same as that used previously in the retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety. 1,213 infants born to 1,140 women (1,142 pregnancies) were exposed to bupropion during the first trimester. The comparison groups consisted of 4,753 infants born to 4,617 women (4,649 pregnancies) exposed to other anti-depressants during the first trimester, and 1,049 infants born to 1,009 women (1,009 pregnancies) exposed to bupropion outside of the first trimester. All medical and prescription claims data along with dates of health plan enrollment for these women were included. The other antidepressant sample was frequency-matched to the bupropion cohort by year of birth, and was selected irrespective of exposure to specific antidepressants.
Key inclusion criteria (7 listed)
- The inclusion criteria will be the same as that used previously in the retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety.
- All deliveries occurring between 01 January 1995 and 30 September 2004 among women ages 12 to 49 who are members of UnitedHealthcare
- Eligible for prescription benefits
- Have one or more dispensings of an antidepressant during the study period
- Continuously enrolled for at least eighteen months prior to delivery
Key exclusion criteria (1 listed)
- Members who are employees of UnitedHealthcare are excluded from the Ingenix Research Database.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3. Exposure to other antidepressants during the first trimester comparison cohortExposure to other antidepressants during first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate dispensing of other antidepressants. Infants were classified according to maternal exposure to other antidepressants during the first trimester. The first trimester was estimated as the earliest probable conception date through 91 days (13 weeks) following the latest probable conception date (based on delivery diagnosis codes). This study will refine the exposure classifications into infants born to women who were exposed only to one type of an antidepressant ("other antidepressant monotherapy"), or more than one type of an antidepressant ("other antidepressant mono or polytherapy") during the first trimester. A woman was considered exposed if there is at least one dispensing of another antidepressant during the first trimester of pregnancy. | Drug | Infants born to women who were exposed to antidepressants |
| 2. Exposure to bupropion outside the first trimester comparison cohortExposure to bupropion outside the first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate a dispensing of bupropion. The comparison cohort ("bupropion exposure outside the first trimester") included women whose bupropion exposure occurred at least one month before the estimated date of conception and women whose bupropion exposure occurred after the first trimester, but before delivery. This study will refine the exposure classifications into infants born to women, who were exposed only to bupropion ("bupropion monotherapy"), or bupropion and another type of an antidepressant ("bupropion mono-or polytherapy") during the period outside the first trimester. | Drug | Infants born to women who were exposed to antidepressants |
| 1. Exposure to bupropion during the first trimesterExposure to bupropion during the first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate a dispensing of bupropion. Infants were classified according to maternal exposure to bupropion during the first trimester. The first trimester was estimated as the earliest probable conception date through 91 days (13 weeks) following the latest probable conception date (based on delivery diagnosis codes). This study will refine the exposure classifications into infants born to women, who were exposed only to bupropion ("bupropion monotherapy"), or bupropion and another type of an antidepressant ("bupropion mono-or polytherapy"). A woman was considered exposed in the first trimester if there was at least one dispensing of bupropion during the first trimester of pregnancy. | Drug | Infants born to women who were exposed to antidepressants |
Primary outcome
Frequencies and prevalence estimates of specific cardiovascular malformations and malformation groupings among live infants born to women exposed to bupropion or antidepressants
Time frame: As performed previously, medical and prescription claims data was assembled and the outcomes of infants in the first 9 months of life were evaluated
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
Questions about this trial
What is this clinical trial studying?
An observational study of Depressive Disorder and Pregnancy, run by GlaxoSmithKline.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequencies and prevalence estimates of specific cardiovascular malformations and malformation groupings among live infants born to women exposed to bupropion or antidepressants (time frame: As performed previously, medical and prescription claims data was assembled and the outcomes of infants in the first 9 months of life were evaluated). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2017; AzTrials last refreshed its copy on 28 Oct 2026.